ABSTRACT There is a lack of evidence that long-term opioid use offers benefit for noncancer pain and an abundance of evidence of harm?. Last year, the Centers for Disease Control and Prevention (CDC) issued the ?CDC Guideline for Prescribing Opioids for Chronic Pain? to encourage safe and effective alternatives to opioids, discontinuation of opioids when patients do not resume normal activities and prudent dosing strategies. However, poor guideline adherence is a general concern and may impede uptake. ?Our prior studies have used insights from behavioral economics and social psychology to increase guideline adherence. We propose to apply these techniques within the Application of Economics & Social psychology to improve Opioid Prescribing Safety (AESOPS) Trial to improve adherence to the CDC and to the Oregon Pain Guidance pain management guideline. In the R21 phase, we will assess the feasibility of implementing the following candidate nudges: 1) Defaults (guideline concordant actions that take place when clinicians fail to act), 2) precommitments (advanced commitments by clinicians to guideline adherent behaviors that bind them to these behaviors in the future), 3) justifications (free-text responses entered by the clinician that explain why guidelines were not followed and which are recorded as a patient note in the electronic health record); these are triggered when defaults are removed and commitments are not honored, 4) peer comparisons (a type of socially motivated performance reporting) and 5) a nudge to increase the salience and availability of adverse opioid events. In the R33 phase, we will conduct the AESOPS trial, an 18-month cluster randomized trial. The trial is across 374 primary care clinics in the U.S. We compare three conditions: C1) Peer comparison and justification , C2) defaults, precommitments or available adverse events added to the C1 interventions, C3) education control. The primary outcomes is clinician aggregate monthly mg morphine equivalent (ME) for patients with ?>?50 mg ME daily dose. Secondary, outcomes are benzodiazepine co-prescribing and rate of dose escalation to ?>?50 mg ME/day. We anticipate that the AESOPS trial will provide new knowledge about how to improve adherence to the CDC Guideline for Prescribing Opioids for Chronic Pain and to concordant pain guidelines. The trial may also help us understand how to prevent future incidents of opioid use disorder and opioid poisoning death by lowering unnecessary population exposure to these drugs.